It is known that lymphocytes exported from the thymus undergo a series of differentiation events which confer upon them the capacity to recognize and respond to specific peptide antigens presented appropriately in the context of self major histocompatibility complex (MHC) molecules. Mechanistically, thymic maturation is a complex process which includes an irreversible rearrangement of T cell receptor genes, the cell surface expression of these gene products as disulfide-linked heterodimers, positive and negative selection processes to provide appropriate restriction and avoidance of self-reactivity, and the synthesis and expression of CD4 or CD8 as accessory adhesion molecules. Microenvironmental influences within the thymus play an essential role in the fidelity of this process.
Subsequent to leaving the thymic microenvironment, mature T lymphocytes gain access to the recirculating T cell pool where they move freely via the blood between mucosal and nonmucosal lymphoid compartments in the mammalian host (Hamann et al. (1989). Immunol, Rev. 108: 19). T-lymphocyte expression of lymphoid tissue-specific homing receptors, which are complementary for vascular addressins on high endothelial venules present in Peyer's patches and peripheral lymph nodes, provide a biochemical means for selectivity to this recirculation process (id.). Non-activated lymphocytes can move freely between mucosal and nonmucosal lymphoid tissues due to the presence of both types of homing receptors on their plasma membranes (Pals et al. (1989). Immunol, Rev, 108: 111). Effector lymphocytes, and antigen-activated immunoblasts which are stimulated in a particular site in the body, however, exhibit a far more selective migratory behavior. These cells move primarily to tissues originally involved in antigen exposure and cellular activation (Hamann et al., supra; Pals et al., supra).
An immune response is initiated following T cell recognition of antigen peptides in the context of self MHC molecules, and generally takes place in one of the host's secondary lymphoid compartments. Cellular activation is triggered by the binding of antigen to the T cell receptor (TCR), forming an antigen/TCR complex which transduces the antigen-specific extracellular stimulation across the plasma membrane, and generates intracellular signals which include the activation of protein kinase C and the increases in intracellular calcium. While signal transduction can lead to T cell unresponsiveness, positive signal transduction events trigger a series of additional biochemical processes. One consequence of this activation is the stimulated production of a number of biologically active molecules, which are collectively termed lymphokines. (See, Alcover et al. (1987). Immunol. Rev, 95: 5; Gelfand et al. (1987). Immunol. Rev. 95: 59).
Vaccines are preparations of antigenic material for administration to induce in the recipient an immunity to infection or intoxication by a given infecting agent. Vaccines may be prepared from viruses, rickettsiae, bacteria, protozoa and metazoa. Vaccines may be sterile suspensions of the killed organisms, of toxoids or other antigenic material derived from the organisms or recombinant sources, which can be administered by injection. Vaccines may be either simple vaccines prepared from one species of organism or a variety of organisms, or they may be mixed vaccines containing two or more simple vaccines. They are prepared in such a manner as not to destroy the antigenic material, although the methods of preparation vary, depending on the vaccine.
Vaccine adjuvants consist of agents that are included in the formulation that are used to enhance the ability of the antigenic material in a vaccine to induce the desired immune response, and with many poorly antigenic materials the success of vaccination depends on the presence of a suitable adjuvant in the vaccine. The adjuvant is sometimes conveniently incorporated in the vaccine before the latter is distributed into containers, although it may be provided in a separate container for mixing with the antigenic material when the vaccine is required for use in immunizing the recipient.
U.S. Pat. No. 4,698,221 discloses a vaccine which contains (a) an antigen, (b) a fat-soluble vitamin, such as Vitamin A, Vitamin D and/or Vitamin E, (c) a zinc compound, and (d) a selenium compound.
DHEA is a steroid hormone that has been extensively studied for many years. It has been reported to be involved in a wide variety of physiologic, immunologic, and pathologic conditions (for reviews, see Regelson et al. (1988). Ann. N.Y. Acad. Sci. 521: 260; Gordon et al. (1986). Adv. Enzyme Reg. 26: 355-382). Most endocrinologists believe that the primary function of DHEA is to serve as a precursor for the synthesis of testosterone and the estrogens by the gonads. Prior to its release into the bloodstream, the vast majority of newly synthesized DHEA becomes sulfated. The conjugated steroid DHEA-S is a secretory product of the adrenal gland in humans and certain primates. DHEA-S represents the major steroid hormone in the circulation of humans, and is converted to DHEA by the enzymatic activity of asteroid sulfatase.
Therapeutic uses for DHEA and certain analogs have been reported for diabetes, dry skin, ocular hypertension, obesity, and retrovital infections. Illustrative of these reports are the disclosures of U.S. Pat. No. 4,395,408, U.S. Pat. No. 4,518,595, U.S. Pat. No. 4,542,129, U.S. Pat. No. 4,617,299, U.S. Pat. No. 4,628,052, U.S. Pat. No. 4,666,898, published European Patent Application No. 0 133 995 A2, and published United Kingdom Patent Application No. GB 2 204 237 A.